Dr Jeff Eaton

Estimates of HIV epidemic trends in sub-Saharan Africa are generated by fitting a simple dynamic epidemic model to national data sources about HIV prevalence in a Bayesian framework, to provide inference about population-wide trends in HIV prevalence, new infections, treatment need and coverage,... Read more

Estimates of HIV epidemic trends in sub-Saharan Africa are generated by fitting a simple dynamic epidemic model to national data sources about HIV prevalence in a Bayesian framework, to provide inference about population-wide trends in HIV prevalence, new infections, treatment need and coverage, and other policy indicators. In this talk I will (1) discuss motivating observations for revisiting the interpretation of widely relied upon data sources for estimating HIV epidemic trends, (2) describe a new integrated demographic projection and HIV epidemic model for improving HIV epidemic trends and projections in sub-Saharan Africa, and (3) investigate the impact of accounting for biases on inferred HIV epidemic incidence trends in sub-Saharan Africa. Finally, I will discuss future opportunities, challenges, and considerations for combing next generation survey data and routine health facility data to generate more granular and real-time HIV estimates.

Stromal cells provide networks on which innate and adaptive immune cells interact. Using a combination of primary human samples, mouse models, in vitro culture systems and computational models we have identified key pathways regulating stromal cell function and remodelling during protective immune responses, immune mediated inflammatory disease (IMID) and cancer. Using both human samples and mouse models we have identified a critical role for IL4 receptor signalling pathway in stromal cells in the development of inflammatory stroma in tertiary lymphoid tissue found in Sjogren’s syndrome and characterised its function in pathological stroma in rheumatoid arthritis, Hodgkin’s lymphoma and metastatic tumours. In contrast gamma interferon receptor signalling in human stromal cells drives a highly regulatory stroma characterised by expression of multiple check-point ligands and inhibitory proteins. Similar to innate immune cells, stromal cells express and respond to localised cues including TLR ligands, inducing rapid topological remodelling modulating the timing and efficacy of immune responses to vaccination, a process dependent on miR132. Thus we propose a model where localised stromal cells in tissues sense and respond to environmental cues (cytokines, pathogen products), differentiating into localised effector stroma that shape the type and duration of tissue specific immune responses. By combining computational simulations with experimental models we have been able to use artificial neural networks to identify a novel therapeutic approaches to modulate stroma-immune cell interactions in established IMIDs and verify the computational predictions using a mouse model of Sjogren’s syndrome. This approach of model driven experimentation has the potential to integrate ‘omics’ and biophysical analysis to accelerate identification of potential therapeutic approaches and biomarkers for the treatment of IMIDs, chronic inflammation, infection and cancer.

Dr Sebastian Funk

Forecasting the course of an outbreak can inform public health planning and decision making. Accurate forecasts, however, are hampered by uncertainty about changes in human behaviour, pathogen genetics and environmental factors that are difficult to capture in real time. I will present a flexible... Read more

Forecasting the course of an outbreak can inform public health planning and decision making. Accurate forecasts, however, are hampered by uncertainty about changes in human behaviour, pathogen genetics and environmental factors that are difficult to capture in real time. I will present a flexible framework based on Bayesian semi-mechanistic models that can be used to incorporate these uncertainties. I will show how we used this to produce regional forecasts during the West African Ebola epidemic of 2014-16, before discussing the applicability of our approach to a wider class of problems. I will conclude with an outlook on the potential for and challenges in using mathematical models to integrate different data sources for understanding and predicting the behaviour of infectious diseases.

Prof Peter Peters

We develop new methods for sample application and vitrification and implement them into a novel platform. The apparatus can be fed with pre-mounted autogrids, circumventing the need for postmounting. For single particle analysis (SPA), minute amount of samples can be applied directly onto a... Read more

We develop new methods for sample application and vitrification and implement them into a novel platform. The apparatus can be fed with pre-mounted autogrids, circumventing the need for postmounting. For single particle analysis (SPA), minute amount of samples can be applied directly onto a supported film. For cellular work, sample carriers with cells grown on them will be exposed to an airknife that removes excess medium. Sample evaporation will be minimized by a feedback loop that maintains the sample near its dewpoint calculated from the ambient temperature and humidity. Vitrification will be accomplished by jet-streaming liquid ethane onto the centre of the grid. I will be happy to share our latest results.

Healthcare professionals across the world are facing increasing pressure because of rising need and demand and stagnant/decreasing resources. Hellish Decisions in Healthcare, now in its third year, is a forum designed to help healthcare professionals navigate the complex and ‘hellish... Read more

Healthcare professionals across the world are facing increasing pressure because of rising need and demand and stagnant/decreasing resources. Hellish Decisions in Healthcare, now in its third year, is a forum designed to help healthcare professionals navigate the complex and ‘hellish decisions’ they need to make to ensure they deliver the best value to the patients and populations they are accountable to. Please join us on January 12-13 at the University of Oxford to learn from and interact with healthcare professionals who have faced problems similar to yours and have used a variety of innovative approaches and strategies to make their hellish decisions.
The conference is hosted by the Value Based Healthcare programme, part of the University of Oxford’s Nuffield Department of Primary Care Health Sciences, in partnership with Better Value Healthcare and the Oxford Health Experiences Institute.
Speakers include:
• Professor Sir Muir Gray CBE, Director of Better Value Healthcare; Chair of Health and Social Care Digital Service.
• Dr Bruno L Holfhof, CEO, Oxford University NHS Foundation Trust
• Sir Andrew Cash OBE, Chief Executive, Sheffield Teaching Hospitals NHS Foundation Trust
• Greg Fell, Director of Public Health, Sheffield
Early bird discounts available. For further information visit www.phc.ox.ac.uk/hellishdecisionsforum

The zinc finger transcriptional repressor B-lymphocyte-induced maturation protein 1 (Blimp1), encoded by the Prdm1 gene, originally cloned as negative regulator of β-interferon gene expression and subsequently identified as a master regulator of plasma cell terminal differentiation, governs cell fate decisions in the developing embryo and adult tissues. In the early embryo, Blimp1 is required to specify the primordial germ cell lineage, and embryos die at midgestation due to an essential requirement in the placenta. Using conditional deletion experiments we have found that Blimp1 activities are essential for morphogenesis of the pharynx, forelimbs and heart. In addition Blimp1 regulates the developmental switch responsible for post-natal reprogramming of the intestinal epithelium. Most recently we have found that Blimp1 identifies a rare population of luminal progenitors in the mammary gland that are essential for morphogenesis and organ homeostasis.

Dr Bin-Zhi Qian

Macrophages are abundantly found in the tumor microenvironment and enhance malignancy. At distal metastatic sites, our previous studies identified a distinct population of metastasis-associated macrophages (MAMs) that promote tumor cell extravasation, seeding and persistent growth. These... Read more

Macrophages are abundantly found in the tumor microenvironment and enhance malignancy. At distal metastatic sites, our previous studies identified a distinct population of metastasis-associated macrophages (MAMs) that promote tumor cell extravasation, seeding and persistent growth. These macrophages were derived from inflammatory monocytes recruited by CCL2/CCR2 chemokine signaling and directly promote tumour cell extravasation through VEGF production. Our recent studies identified two subsequent signaling pathways that mediate the retention and function of MAMs after recruitment that are critical for tumour cell survival and persistent growth. Specifically, activation of CCR2 signaling turns on CCL3 expression in MAMs. Genetic deletion of CCL3 or its receptor CCR1 in macrophages reduces lung metastasis, and MAM accumulation in tumor-challenged lung. Adoptive transfer of wild type monocytes restores lung metastasis in Ccl3 deficient mice. Mechanistically, Ccr1 deficiency prevents MAM retention in the lung by reducing direct MAM–tumour cell interactions. On the other hand, MAMs turn on cell surface expression of FMS-like tyrosine kinase 1 (FLT1) upon differentiation from monocytes. Using several genetic models of Flt1 deficiency, we show that macrophage specific FLT1 signaling is critical for breast tumor distal metastatic potential. FLT1 specific inhibitory antibody significantly inhibits the metastatic seeding and persistent growth but does not affect the recruitment or retention of MAMs. Furthermore, we identified that FLT1 signaling regulates a set of downstream inflammatory response genes including Colony Stimulating Factor 1 (CSF1) a central regulator of macrophage biology. Using a genetic gain-of-function approach we show that CSF1 mediated autocrine signaling in MAMs is downstream of FLT1 and can restore the tumor-promoting activity in MAMs even when FLT1 is inhibited. Together, our data indicates CCL3/CCR1 and FLT1 signalling pathways are critical in regulating MAMs and promoting breast cancer distal metastasis, and suggests the therapeutic potential of targeting these pathways in treating metastatic disease.

Professor Jeffrey Sachs

The Emerging Markets Symposium (EMS) was created in 2008 as an academic initiative of Green Templeton College (GTC). The EMS is an expression of GTC’s commitment to promote understanding of the issues of managing human welfare in the modern world and the flow of ideas across traditional... Read more

The Emerging Markets Symposium (EMS) was created in 2008 as an academic initiative of Green Templeton College (GTC). The EMS is an expression of GTC’s commitment to promote understanding of the issues of managing human welfare in the modern world and the flow of ideas across traditional disciplinary and professional boundaries.
Jeffrey Sachs, University Professor, Quetelet Professor of Sustainable Development and Professor of Health Policy and Management at Columbia University will deliver a lecture on Friday 13 January, 6pm, on the 2017 EMS theme of Health and the Environment in Emerging Markets. Professor Sachs is the recipient of numerous awards and honours, a prolific author and journalist and is widely regarded as one of the world’s most influential authorities on relationships between health and the natural and built environments.

Sonia Ehrlich Sachs

Sonia Ehrlich Sachs will speak on Health systems in low income setting as part of the Global Health Policy Programme. Sonia Ehrlich Sachs is a pediatrician and public health specialist. She received a B.A. from Harvard University, an M.D. from the University of Maryland Medical School, and an MPH... Read more

Sonia Ehrlich Sachs will speak on Health systems in low income setting as part of the Global Health Policy Programme. Sonia Ehrlich Sachs is a pediatrician and public health specialist. She received a B.A. from Harvard University, an M.D. from the University of Maryland Medical School, and an MPH from Harvard School of Public Health. A pediatrician with a specialty in pediatric endocrinology, Sonia practiced medicine for over 20 years, 14 of which she spent at the Harvard University Health Services. In 2004 she joined the Earth Institute and became the health coordinator for the Millennium Villages Project overseeing all health related interventions and research. The Millennium Villages Project is proof of concept that extremely poor rural communities can reach the Millennium Development Goals given a science-based, community led approach of integrated interventions that increase food production and increase access to health care, education, water and infrastructure. The goal is to show that such an integrated development approach is both scalable and sustainable.

Prof Peter McNaughton

The HCN4 ion channel is well known for driving pacemaker activity in the heart and thus modulating the heart rate. The McNaughton lab has discovered that HCN2, a different member of the same family, plays a similar role in nerve fibres. When HCN2 is activated by inflammatory mediators released... Read more

The HCN4 ion channel is well known for driving pacemaker activity in the heart and thus modulating the heart rate. The McNaughton lab has discovered that HCN2, a different member of the same family, plays a similar role in nerve fibres. When HCN2 is activated by inflammatory mediators released following tissue damage, then the firing of nerve action potentials is potentiated in nerve fibres which transmit the sensation of pain. Blocking the HCN2 ion channel may therefore provide analgesia, but blockers must be highly selective to avoid blocking the HCN4 ion channel which drives the heartbeat. We have found that HCN2-selective blockers can deliver remarkable analgesia in animal pain models, and thus may offer effective analgesia in poorly treated pain conditions such as neuropathic pain, an intractable pain condition caused by nerve damage. In more recent work we have found that HCN2 ion channels expressed in the auditory nerves may also be the drivers of tinnitus, another common and distressing condition associated with nerve damage.

Dr Steve Pollard

Neural stem cells produce the neurons and glial cells that make up our nervous system. They can be expanded continuously in the laboratory, thereby providing an unlimited source of human cells for disease modelling and regenerative medicine.
Cells that have molecular hallmarks of neural stem cells... Read more

Neural stem cells produce the neurons and glial cells that make up our nervous system. They can be expanded continuously in the laboratory, thereby providing an unlimited source of human cells for disease modelling and regenerative medicine.
Cells that have molecular hallmarks of neural stem cells drive human brain cancers, such as glioblastoma. A full understanding of the molecular and cellular events that control neural stem cell fate may therefore reveal new therapeutic strategies to treat this devastating disease.
We are exploiting the latest experimental tools of molecular and cellular biology to address the following questions: How do neural stem cells make the decision to make more copies of themselves (self-renew), or become specialised (differentiate)? Why do brain tumour stem cells display unconstrained self-renewal? Are those genes and pathways that initiate and maintain neural stem cell identity useful therapeutic targets for glioblastoma? Can we identify new drugs that can specifically block self-renewal of brain tumour stem cells?

Dr Lorelei Jones

Abstract
There is growing recognition of the limitations of realist evaluation, and other theory driven approaches to evaluation, in the context of healthcare policies. These approaches, which seek to surface ‘programme theories’ or construct ‘logic models’, are often unable to account for... Read more

Abstract
There is growing recognition of the limitations of realist evaluation, and other theory driven approaches to evaluation, in the context of healthcare policies. These approaches, which seek to surface ‘programme theories’ or construct ‘logic models’, are often unable to account for empirical observations of policy implementation in real-life situations. In this talk, Lorelei will discuss previous work with Justin Waring, to argue that this failure stems from insufficient theoretical elaboration of the social, cultural, and political dimensions of healthcare policies. Drawing from institutional theory, critical theory and discourse theory, and from organizational ethnography, they have set out an alternative approach to research on healthcare reform. Lorelei will illustrate this with examples from their experience of research on acute care ‘reconfiguration’, integrated health and social care and other forms of major system change in the NHS in England.
Biography
I am an anthropologist in the UCL Department of Applied Health Research. My research looks at the changing social organisation of health care services and professional work in the context of contemporary policy reforms. My doctoral research was an ethnographic study of the politically contested issue of hospital planning. I am currently interested in the role of expertise in governing, using policies for ‘major system change’ and the practices of policy evaluation as particular cases. I am a member of the editorial board for Sociology of Health and Illness, and co-convenor of the London Medical Sociology Group where we explore the links between social theory, philosophy and medical sociology.

Dr C.J.S. Hassall

Candy Hassall provides expert support to prospective applicants, Wellcome Trust-funded researchers and, importantly, the members of their teams. She is also working with others to develop a programme of activities to enhance the Wellcome’s support for the people we fund. She held a British Heart Foundation Basic Science Lectureship at University College London before joining the Trust in 1996.

Candy Hassall provides expert support to prospective applicants, Wellcome Trust-funded researchers and, importantly, the members of their teams. She is also working with others to develop a programme of activities to enhance the Wellcome’s support for the people we fund. She held a British Heart Foundation Basic Science Lectureship at University College London before joining the Trust in 1996.

Associate Professor Tove Fall

Recent technical developments have enabled large-scale molecular analyses of biological samples, such as the assessment of plasma metabolomics and proteomics. Some of these compounds have been found to be either increased or decreased in individuals with diabetes and pre-diabetes, but it is unclear... Read more

Recent technical developments have enabled large-scale molecular analyses of biological samples, such as the assessment of plasma metabolomics and proteomics. Some of these compounds have been found to be either increased or decreased in individuals with diabetes and pre-diabetes, but it is unclear whether these aberrations are part of the pathogenesis. We and others have applied bi-directional Mendelian Randomization methods in population-based cohorts and public genetic association data of metabolomics and glycemic traits to try to disentangle the causal directions. Given the vast effects of insulin on the metabolism, it is not surprising to find genetic evidence that several of these aberrations are secondary to insulin resistance. In many cases, however, especially for lipid metabolites, it has been difficult to find specific genetic instruments to assess causality.

Dr Siim Pauklin

Dr Pauklin studies the molecular mechanisms that govern the stem cell identity of human pluripotent stem cells, and their relevance to tumorigenic processes. He is particularly interested in the function of TGFß/Nodal-Smad2/3 signalling pathway, which has a central role in maintaining pluripotent... Read more

Dr Pauklin studies the molecular mechanisms that govern the stem cell identity of human pluripotent stem cells, and their relevance to tumorigenic processes. He is particularly interested in the function of TGFß/Nodal-Smad2/3 signalling pathway, which has a central role in maintaining pluripotent stem cells and cancer stem cells. Dr Pauklin’s talk will focus on his recent discoveries on cell cycle and epigenetic mechanisms that regulate the self-renewal and differentiation of human pluripotent stem cells (Pauklin 2013 Cell; Pauklin 2016 Genes Dev; Bertero 2015 Genes Dev).

Prof Keith Willet

Professor Keith Willett is the Medical Director for Acute Care to NHS England and is the Professor of Orthopaedic Trauma Surgery at the University of Oxford. An NHS consultant surgeon for 24 years he has extensive experience of trauma care, driving service transformation and healthcare management. He has taught surgery and clinical leadership extensively across the NHS and internationally.

Professor Keith Willett is the Medical Director for Acute Care to NHS England and is the Professor of Orthopaedic Trauma Surgery at the University of Oxford. An NHS consultant surgeon for 24 years he has extensive experience of trauma care, driving service transformation and healthcare management. He has taught surgery and clinical leadership extensively across the NHS and internationally.

Dr Diana Quirmbach

With the global prevalence of obesity rising, fiscal measures to reduce the consumption of energy-dense foods, and particularly sugar-sweetened beverages (SSB), are being advocated and implemented in many countries. In the UK, the government has proposed an industry levy on SSBs to be implemented... Read more

With the global prevalence of obesity rising, fiscal measures to reduce the consumption of energy-dense foods, and particularly sugar-sweetened beverages (SSB), are being advocated and implemented in many countries. In the UK, the government has proposed an industry levy on SSBs to be implemented in 2018. However, even if the levy were to be passed through fully and result in higher prices for SSBs, the overall health impact depends on the complement and substitution relationships across the whole diet. An aspect that receives less attention is the contribution of consumption of alcoholic beverages on the energy intake of households, with beer and wine providing on average 43 and 85 kilocalories per 100 ml, respectively; in comparison to an average of 40 kcal in 100 ml of Cola drink. Limited references in the literature are available considering alcohol consumption from the energy intake perspective, but it is not clear how public health policies targeting either the price of non-alcoholic or alcoholic beverages affect the consumption of alcoholic drinks vis-à-vis SSBs. In this paper we draw on a comprehensive dataset of individual purchases of food and drinks for 30,000 households in the UK (2012-2013) which allows us to estimate the own- and cross-price elasticities for SSBs, considering alcoholic and non-alcoholic drinks. Overall, households in the sample on average spent £17.5 and £10.3 per month on alcoholic and non-alcoholic drinks respectively. However, the share of households who never purchased a particular drink category ranged from 16% for fruit juices to more than 50% for certain alcoholic drinks such as cider or sparkling wine. The estimated demand model will account for (i) censoring of expenditure at zero, (ii) endogeneity of prices and expenditure, as well as (iii) unobserved heterogeneity at the household level.

Dr Lucie Bruijn

Lucie Bruijn, Ph.D. joined The ALS Association in January 2001 and is currently the Chief Scientist. Prior to that Dr. Bruijn led a team at Bristol Myers Squibb developing in vitro and in vivo model systems for neurodegenerative disease. Realizing the potential of stem cell therapy for... Read more

Lucie Bruijn, Ph.D. joined The ALS Association in January 2001 and is currently the Chief Scientist. Prior to that Dr. Bruijn led a team at Bristol Myers Squibb developing in vitro and in vivo model systems for neurodegenerative disease. Realizing the potential of stem cell therapy for neurodegenerative diseases, her team worked with experts in academia to establish stem cell studies at Bristol Myers Squibb.
At The ALS Association, Dr. Bruijn leads a global ALS research effort, Translational Research to Advance Therapies for ALS (TREAT ALS™) with the goal to move treatment options from “bench to bedside.” She has made it a priority to collaborate with other funding agencies, in particular The National Institutes of Health, The Department of Defense and many other not-for-profit ALS organizations, as well as other foundations focusing on neurodegenerative research. These collaborations ensure that increased dollars are spent on ALS research. She is involved in project development, encouraging partnerships with academia and biotech, and has played a key role in forging collaborations amongst investigators. It is her strong belief that only through collaboration among a wide range of disciplines will we be successful in changing the course of ALS and finding a cure.

Prof Emmanuel Reynaud

The Moon has been visited many times by mankind while the Marianna Trench has been seen once. Our wishes to understand the complexity of the biological world remains at the surface. Since many years our gathering of biological data has been limited to a handful of model systems often biased by the... Read more

The Moon has been visited many times by mankind while the Marianna Trench has been seen once. Our wishes to understand the complexity of the biological world remains at the surface. Since many years our gathering of biological data has been limited to a handful of model systems often biased by the way they are grown or even imaged. But nowadays, mobile phone technology and newly established 3D imaging techniques allows us to step out of the laboratory to look at the biological world as it is. Through scientific expeditions (e.g. Tara Oceans 2009-2012) and collaborations we have been going into the wild to record underwater coral reefs and integrate the collected data at different scales from the reef to the museum and back. This unique approach allows us to also establish online automated taxonomical systems to collect scientific data without collecting and fixing organism using statistical deformations models that could become reference 3D models in research laboratories and database such as GenBank. Furthermore we can 3D print the models creating a Digital Ocean that can be replicated anywhere in an effort to preserve the largest biotope on Earth but also to give the opportunity to bench-bound scientists to explore the third dimension in its full.

Professor Gina Neff

Abstract
Today smartphones and wearable devices help people to self-track: hours slept, steps taken, calories consumed, medications administered. Technology producers shipped over one hundred million wearable sensors in 2016. However, scholars do not yet understand how -- or if -- digital... Read more

Abstract
Today smartphones and wearable devices help people to self-track: hours slept, steps taken, calories consumed, medications administered. Technology producers shipped over one hundred million wearable sensors in 2016. However, scholars do not yet understand how -- or if -- digital self-tracking works to promote positive behaviour change for health, much less the social and political ramifications of self-tracking for reshaping norms, protocols, and policies for health and wellness. This talk reports results from a comparative study of the practices around self-tracking data among fitness advocates, elderly chronically ill patients in a telehealth programme, and primary care physicians. I use the findings from this research to motivate five key propositions for using self-tracking data to launch innovation in healthcare. I do so by bringing the tools of sociological theory and methods to understanding how people recorded, analyse, and reflect on data about themselves; by drawing lessons from the early adopters of ‘Quantified Self’ tools, practices, and communities; and by mapping the discourses about data among multiple stakeholder communities in healthcare. Can such data be used in a way that empowers and educates the people whose bodies generate it? Can self-tracking data be used to support patient involvement in the innovation of healthcare? What critical infrastructure needs to be put in place so that self-tracking of health does not cause harm to patients? The answers, I will argue from looking at cases of conflict over self-tracking data, will depend largely on technologies and policies for self-tracking health data that are being designed now.
Biography
Professor Gina Neff is a Senior Research Fellow at the Oxford Internet Institute and an Associate Professor in the Department of Sociology at the University of Oxford. She studies innovation, the digital transformation of industries, and how new technologies impact work.
She has published three books and over three dozen research articles on innovation and the impact of digital transformation. Her book Venture Labor: Work and the Burden of Risk in Innovative Industries (MIT Press, 2012) about the rise of internet industries in New York City, won the 2013 American Sociological Association Communication and Information Technologies Best Book Award. Her book, Self-Tracking, co-authored with Dawn Nafus (MIT Press, 2016) focuses on the practices and politics of using consumer technologies to track health and other everyday personal metrics. Her ongoing project on large-scale building architecture and construction examines how new information and communication technologies require new ways of working and the challenges of implementing these changes at an industrial scale.
She holds a Ph.D. in sociology from Columbia University where she remains a faculty affiliate of the Center on Organizational Innovation. Professor Neff has held faculty appointments at the University of Washington and the University of California, San Diego. She has had fellowships at the Institute for Advanced Study and the Center for Information Technology Policy. Her popular writing has appeared in Wired, The Atlantic, and Slate.
For more information, please contact Chrysanthi Papoutsi (chrysanthi.papoutsi@phc.ox.ac.uk)

Dr Jan Rehwinkel

The innate immune response is critical for successful host defence against virus infection. Cell-intrinsic mechanisms detect virus presence and restrict virus replication. Nucleic acids are often a molecular signature of virus infection and are recognised by innate receptors including toll-like... Read more

The innate immune response is critical for successful host defence against virus infection. Cell-intrinsic mechanisms detect virus presence and restrict virus replication. Nucleic acids are often a molecular signature of virus infection and are recognised by innate receptors including toll-like receptors, RIG-I-like receptors and cytosolic DNA sensors. These receptors signal for the induction of innate response genes such as those encoding type I interferons. These in turn induce the expression of restriction factors, host proteins that limit virus replication.
Our work focuses on cytosolic nucleic acid sensors, in particular RIG-I, MDA5 and cGAS. We are also studying the restriction factor SAMHD1. We are using in vitro and in vivo models of virus infection (including influenza A virus, retroviruses and varicella-zoster virus) and are interested in Aicardi-Goutières syndrome, a rare genetic disease linked to chronic anti-viral innate immune responses. In this presentation, I will discuss our recent work on cGAS and other nucleic acid sensors.

Dr Vincenzo Costanzo

Coordination between DNA replication and DNA repair ensures maintenance of genome integrity, which is lost in cancer cells. Lesions and discontinuities in the DNA template undergoing replication induce replication fork stalling. Homologous recombination (HR) proteins RAD51 and BRCA1/2 play a major... Read more

Coordination between DNA replication and DNA repair ensures maintenance of genome integrity, which is lost in cancer cells. Lesions and discontinuities in the DNA template undergoing replication induce replication fork stalling. Homologous recombination (HR) proteins RAD51 and BRCA1/2 play a major role in the stability of replication forks. This function appears to be distinct from the classical one performed by these proteins in HR dependent DNA Double Strand Break repair. Using Xenopus laevis egg extract we discovered that RAD51 prevents MRE11 mediated degradation of nascent DNA at stalled forks in eukaryotic cells. This finding has been widely confirmed in different model systems. The use of electron microscopy mediated analysis of replication intermediates is allowing the dissection of several mechanistic aspects of HR proteins function in replication fork protection. I will address the crosstalk between BRCA1/2, RAD51 and the MRE11 complex in light of our more recent findings.

Integration of clinical metabolomic profiling with interpretation of genetic variants improves diagnosis of rare disease
Sarah H. Elsea, Ph.D. FACMG
Senior Division Director, Biochemical Genetics
Dept. of Molecular and Human Genetics
Baylor College of Medicine
Houston, TX USA
Metabolomics is the study of the distinctive chemical fingerprint produced by specific cellular processes. Untargeted mass spectrometry-based metabolomics profiling for small molecules in body fluids, including urine, plasma, and cerebrospinal fluid, is an emerging technique used to produce and analyze this chemical fingerprint. This technology holds the promise of providing new insights into human disease states and serving as a primary diagnostic tool for novel and previously characterized inborn errors of metabolism (IEM), as well as for the identification of biomarkers of disease and treatment. Clinical metabolomic profiling is a novel platform that allows for parallel testing of hundreds of metabolites in a single biological specimen. Using a state-of-the-art mass spectrometry platform, the resulting spectra are compared against a library of ~2,500 human metabolites. On average, ~800 small molecules are detected in a given plasma sample with a core group of ~350 analytes found in all specimens tested to date. The analytes detected encompass numerous classes of important small molecule biomarkers including acylcarnitines, amino acids, bile acids, carbohydrates, lipids, and nucleotides. In addition, metabolomic data in many cases affords a much richer view of a patient's metabolic disturbance by identifying: (1) elevated metabolites located far upstream of the genetic defect, (2) treatment related compounds, including commonly tested therapeutic drug monitoring analytes, and (3) spectrally unique analytes that are not yet associated with a biochemical phenotype. In our clinical experience, the integration of whole exome sequencing data with the metabolomics profile has improved the interpretation of genetic variants, including ruling out the diagnosis of IEMs, as well as supporting a specific diagnosis, and for the identification of new disease biomarkers. For the undifferentiated genetic phenotypes such as intellectual disability, autism, or seizures, often many different tests involving different sample types are needed for diagnosis. This can lead to prohibitive costs and ongoing diagnostic odysseys. Utilizing clinical metabolomics alone as a broad screening tool has also resulted in several diagnoses, typically expanding the phenotypes of those disorders. Our experience with metabolomic profiling of previously nondiagnostic cases has led to the diagnosis of genetic disorders such as GABA transaminase deficiency, aromatic amino acid decarboxylase deficiency, and adenylosuccinate lyase deficiency, illustrating the powerful synergy of metabolomic and genomic analyses in determining the pathogenicity of variants of uncertain significance, as well as broadening the phenotypic spectrum of each disorder. Ultimately, a clinical systems biology approach to the integration clinical data with genomic, transcriptomic, epigenomic, proteomic, and metabolomics data will provide a better understanding of natural biological variation toward improved diagnosis.

Dr Nic Tapon

Polarity is a shared feature of most cells. In epithelial tissues, apical-basal polarity often coexists, and sometimes intersects with, planar cell polarity (PCP), which orients cells in the plane of the epithelium. From a limited set of core building blocks (e.g. the Par complexes for apical-basal... Read more

Polarity is a shared feature of most cells. In epithelial tissues, apical-basal polarity often coexists, and sometimes intersects with, planar cell polarity (PCP), which orients cells in the plane of the epithelium. From a limited set of core building blocks (e.g. the Par complexes for apical-basal polarity and the Frizzled/Dishevelled complex for PCP), a vast array of polarized cells, tissues and organs are generated. This suggests the existence of little-studied tissue-specific factors that rewire the core polarity modules to produce the appropriate polarized structure. I will discuss our latest work on Meru, which functions as a polarity remodelling factor in asymmetric cell divisions in Drosophila.

Dr Robert Köechl

I grew up in Austria and studied Biology at the University of Innsbruck. For my diploma thesis, I went to Berlin where I worked in Ralf Schülein’s group at the Research Institute of Molecular Pharmacology investigating the intracellular transport of G-protein coupled receptors. After finishing... Read more

I grew up in Austria and studied Biology at the University of Innsbruck. For my diploma thesis, I went to Berlin where I worked in Ralf Schülein’s group at the Research Institute of Molecular Pharmacology investigating the intracellular transport of G-protein coupled receptors. After finishing my degree, I moved to London to study for my PhD in Sharon Tooze’s lab at Cancer Research UK’s London Research Institute, where I studied the fusion mechanisms of autophagosomes with early and late endosomes. Keeping in line with my interest in signaling and cell biology I then started as a postdoc in Victor Tybulewicz’s lab at the MRC National Institute for Medical Research - now the Francis Crick Institute - to work on the role of kinases in T cell biology.

Miriam Frankel

Want to raise the profile of your research and engage with the wider public? Come along to find out how you can get involved in The Conversation and get top tips about writing expert opinion articles from their technology editor.
The University of Oxford has recently become a member of The... Read more

Want to raise the profile of your research and engage with the wider public? Come along to find out how you can get involved in The Conversation and get top tips about writing expert opinion articles from their technology editor.
The University of Oxford has recently become a member of The Conversation – an online source of thought-provoking articles written by researchers and academics for the public in the UK and globally.
The articles are often picked up by other media (e.g. the BBC, The Guardian, The Washington Post). To date, over 200 Oxford researchers and academics have published articles attracting 8 million readers from across the world.
OBJECTIVES: – Increase awareness of what The Conversation is – Increase awareness and understanding of how to get involved in The Conversation – Increase and reinforce understanding of basic concepts of writing effective opinion articles for the public

Miriam Frankel

Want to raise the profile of your research and engage with the wider public? Come along to find out how you can get involved in The Conversation and get top tips about writing expert opinion articles from their technology editor.
The University of Oxford has recently become a member of The... Read more

Want to raise the profile of your research and engage with the wider public? Come along to find out how you can get involved in The Conversation and get top tips about writing expert opinion articles from their technology editor.
The University of Oxford has recently become a member of The Conversation – an online source of thought-provoking articles written by researchers and academics for the public in the UK and globally.
The articles are often picked up by other media (e.g. the BBC, The Guardian, The Washington Post). To date, over 200 Oxford researchers and academics have published articles attracting 8 million readers from across the world.
OBJECTIVES: – Increase awareness of what The Conversation is – Increase awareness and understanding of how to get involved in The Conversation – Increase and reinforce understanding of basic concepts of writing effective opinion articles for the public

Dr. Julian Sale

Led by two professional radio producers with over 40 years of pitching and documentary-making experience between them, this session will offer insider insights into radio, and how to pitch your ideas to BBC networks. Participants will be sent details regarding the deadlines for submission of... Read more

Led by two professional radio producers with over 40 years of pitching and documentary-making experience between them, this session will offer insider insights into radio, and how to pitch your ideas to BBC networks. Participants will be sent details regarding the deadlines for submission of pitches.
The following questions will be addressed in a workshop setting: how does radio 'work'?; what is pitching?; how might I turn my research into a radio programme?; what are radio commissioners looking for? The workshop leaders will present practical information relating specifically to BBC Radio 4, including relevant contacts and pitching deadlines.
Competition for Radio 4 commissions is fierce, with thousands of ideas pitched from all over the UK (and further afield) for a small number of available programmes each year. Despite this, over the two previous years that these sessions have been run there have been two successful commissions with Radio 4 and one with the World Service. In addition, one idea has featured on Something Understood on Radio 4.
Open to all researchers in MPLS and Medical Sciences Divisions, from DPhil students upwards.